Forty-One Individuals With Mutations in the AVP-NPII Gene Associated With Familial Neurohypophyseal Diabetes Insipidus.
J Clin Endocrinol Metab
; 105(4)2020 04 01.
Article
in En
| MEDLINE
| ID: mdl-32052034
ABSTRACT
CONTEXT Familial neurohypophyseal diabetes insipidus is a rare disease produced by a deficiency in the secretion of antidiuretic hormone and is caused by mutations in the arginine vasopressin gene. OBJECTIVE:
Clinical, biochemical, and genetic characterization of a group of patients clinically diagnosed with familial neurohypophyseal diabetes insipidus, 1 of the largest cohorts of patients with protein neurophysin II (AVP-NPII) gene alterations studied so far.DESIGN:
The AVP-NPII gene was screened for mutations by PCR followed by direct Sanger sequencing in 15 different unrelated families from Spain.RESULTS:
The 15 probands presented with polyuria and polydipsia as the most important symptoms at the time of diagnosis. In these patients, the disease was diagnosed at a median of 6 years of age. We observed 11 likely pathogenic variants. Importantly, 4 of the AVP-NPII variants were novel (p.(Tyr21Cys), p.(Gly45Ser), p.(Cys75Tyr), p.(Gly88Cys)).CONCLUSIONS:
Cytotoxicity seems to be due to consequences common to all the variants found in our cohort, which are not able to fold correctly and pass the quality control of the ER. In concordance, we found autosomal dominant familial neurohypophyseal diabetes insipidus in the 15 families studied.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Precursors
/
Neurophysins
/
Vasopressins
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Genetic Predisposition to Disease
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Diabetes Insipidus, Neurogenic
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Mutation
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
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Adult
/
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
/
Middle aged
Language:
En
Journal:
J Clin Endocrinol Metab
Year:
2020
Document type:
Article
Affiliation country:
Spain